Repairing the Brain after Stroke

Stroke is one of the most prevalent and debilitating diseases on the planet. With a critical shortage of therapeutic options for stroke patients, who often suffer from lifelong motor and cognitive deficits, there is an exceptional need for research into the mechanisms of brain damage and repair, both at the acute and post-acute phases after stroke. The Steinberg lab’s long-term goal is to exploit these repair pathways in order to develop therapeutics that both minimize damage from stroke as well as improve function in those who are living with the aftermath of stroke.

Some spontaneous recovery often occurs in the brain days and weeks after stroke. Understanding how this happens will help us develop interventions that maximize these naturally-occurring repair mechanisms. We now know that multiple processes are involved, including plasticity (or reorganization of neural connections and pathways), inflammation and angiogenesis. Several approaches of study are therefore required to understand individual mechanisms of action as well as how they work in concert to improve recovery. Our approaches include optogenetics at the circuit level, electrophysiology and array tomography at the synaptic level and behavioral testing at the systems level.

As transplanted neural stem cells offer tremendous promise in promoting recovery after stroke, we also study how they enhance recovery in animal models of stroke. We use genetic mouse models, gene profiling and gene transfer techniques to study how they modulate brain plasticity, as well as other repair pathways related to angiogenesis and inflammation. Identifying the molecular mechanisms of stem-cell-mediated brain recovery after stroke will enable us to manipulate the system to optimize stem cell efficacy, and could also lead to the identification of novel drug targets for stroke.

Understanding Moyamoya (MMD) Disease

We study moyamoya disease (MMD) and arteriovenous malformations (AVMs), poorly understood rare vascular diseases that can cause debilitating ischemic and hemorrhagic strokes. To better understand the etiology of these diseases, we use tissue and biofluids donated by patients treated at our extensive clinical MMD and AVM programs. Using techniques as diverse as exome sequencing, gene profiling and immunohistochemistry, these studies have already revealed unique disease-specific genetic and protein changes. Our findings will help inform future studies on elucidating disease mechanisms using cells, tissue, and animal models, as they are developed, and help develop criteria for evaluating hemorrhage risk and guiding treatment.